by Laura Ungar, The (Louisville, Ky.) Courier-Journal

The plight of such women inspired a team of doctors from Louisville, Ky., and Kolkata in 2007 to explore a new treatment for the potentially deadly disease.

But that team is now reaching a disappointing conclusion: An experimental radiation and immunotherapy regimen appears less effective against advanced cancer than the traditional Western treatment, which remains out of reach for many poor, Indian women.

"The data show that chemo and radiation, which is the consensus way to treat advanced cervical cancer in the States," seems to work better than the experimental treatment among the Indian patients, said University of Louisville researcher Dr. A. Bennett Jenson.

"I was (initially) under the notion it was as effective as chemo. And I don't think it is," said Jenson, of the James Graham Brown Cancer Center. "I'm disappointed. It wasn't the answer we wanted. ... (But) seventy-five percent of clinical trials don't yield the results you want them to yield."

Initial results from the five-year study at India's Chittaranjan National Cancer Institute looked promising, with the experimental regimen accounting for slightly more recoveries than the conventional treatment two years into the study.

Hopes were high that the experimental regimen might help impoverished women around the world, including in rural, low-income areas.

But now, nearly a year after the last woman enrolled, the results have become discouraging.

Of 103 women in the experimental arm of the trial, 42 are free of disease, six are alive with recurrent disease, and 55 have died. Of the 106 women in the control arm - those treated with conventional treatment - 61 are free of disease, 10 are alive with a recurrence, and 35 have died.

Cervical cancer at late stages is uniformly fatal if left untreated, and even with chemo-radiation treatment, the five-year survival rate is 50 percent or less.

As of now, "the study shows the immunotherapy does not have any advantage over the conventional chemo-radiation," said Dr. Partha Basu, head of the department of gynecological oncology at Chittaranjan and principal investigator in the study.

"I wish the immunotherapy arm would have done a little better. I really wanted it to work better for the patients," said Debapriya Banerjee, clinical trials manager for gynecological oncology at Chittaranjan.

Basu stressed that they are still following up with patients, and questions remain - including some that raise doubt about whether the difference in deaths is statistically significant and will hold up over the long term.

For example, he said, more women who joined the study early were placed into the experimental arm, meaning they've had more time for relapses and death to occur than those in the control arm. Also, he said, it's been difficult to determine what has happened to every participant, since some women never returned from remote villages for follow-up.

No matter what they find, Basu and Jenson said there's an undeniable upside to the study: a commitment to providing more patients with chemotherapy.

Before 2007, Basu said most Chittaranjan patients with advanced cervical cancer received only radiation because there weren't enough hospital beds for chemotherapy.

"As we started providing chemotherapy through the trial, more patients started demanding chemotherapy," Basu said, resulting in a day chemotherapy center opening at the hospital.

Deadly in India

Basu and Jenson said the study also underscores the need for cervical cancer prevention.

Jenson, one of the inventors of the Gardasil shots that protect against the human papillomavirus that causes most cervical cancer, is now working on an inexpensive version for the developing world that would cost as little as $3.

Basu, meanwhile, has become more involved in improving cervical cancer detection and awareness, partly through "screening camps" in remote areas. He recently operated on 50-year-old Neburjan Bibi, who lives in a village seven hours from Kolkata and whose early-stage cancer was discovered at a screening camp.

"The chance of recurrence is very low," Basu said, touching Bibi's arm as she lay in a hospital bed. "She'll be OK."

Cervical cancer is both preventable and curable at early stages. Yet it remains the biggest cancer killer of Indian women, striking 130,000 each year and killing 75,000.

Poverty, combined with a lack of cervical cancer screening and access to health care, means the vast majority of cases are diagnosed late.

In the United States, women are routinely screened for cervical cancer with Pap smears and often have precancerous lesions removed before they turn into cancer. About 12,000 American women are diagnosed with cervical cancer each year, and about 4,000 die.

A study released in 2009 by the World Health Organization found that Indian women have a lower rate of infection from human papillomavirus, or HPV, than Americans.

But Indians face risk factors Americans don't. For example, village women often marry in their teens and get pregnant soon afterward, which suppresses immune systems weakened by malnutrition and increases the likelihood that an HPV infection will progress to cancer.

And once cancer strikes, getting care can be difficult for the poor, rural women who are hardest hit. There are fewer than a third as many hospital beds per person in India as in the United States, and many rural villages are hours from hospitals.

A new approach

The Louisville-Kolkata trial, which began enrolling women in the fall of 2007, randomly assigned participants with advanced cancer to the chemotherapy-radiation control group or the study group.

Those in the study group got radiation plus immunotherapy consisting of pills of retinoic acid, a derivative of Vitamin A; and shots of the protein interferon-alpha. When recruiting subjects, doctors said they emphasized the experimental nature of the regimen.

This wasn't the first trial to test the treatment; it had shown promise in three of four pilot studies elsewhere. But researchers said it is the first time it was tested in untreated women with cancer as advanced as the majority of cases in India.

Doctors said both treatments cost about the same. Treatment medications and hospital care are free to participants, and Jenson personally donated $5,000 for other medicines that patients in the trial might need.

Basu said there were fewer side effects among women in the experimental arm of the trial. And two years into the trial, 69 of the 114 who had enrolled were disease-free, with the experimental arm accounting for a greater number of disease-free patients than the control arm.

But over the next few years, cancer returned among more patients taking the immunotherapy treatment than in those receiving traditional chemotherapy.

Prevention effort

As chief coordinator of the Cervical Cancer Prevention & Control Initiative, a partnership among Chittaranjan, the medical testing company Qiagen of Germany, and the ministry of health in West Bengal, the state where Kolkata is located, Basu said he is focused now on trying to head off cervical cancer before it starts.

His efforts include working with several nongovernmental organizations, training field workers to raise awareness in their communities and using a Qiagen HPV test to screen for pre-cancers among women in remote areas.

Meanwhile, research on a new HPV vaccine continues in Louisville.

Jenson and colleagues are looking at using Kentucky tobacco to develop the inexpensive vaccine and hope to have a federally approvable version within two years.

"What we want more than anything is to deliver an economically viable vaccine that can be used in places like India," Jenson said. "If we are successful with this, Partha would be the first person to vaccinate women. And I would hope to go there to see the first person be vaccinated."